Secretion of interleukin-10 or interleukin-12 by LPS-activated dendritic cells is critically dependent on time of stimulus relative to initiation of purified DC culture

Hui-Rong Jiang, Elizabeth Muckersie, Marie Robertson, Heping Xu, Janet Mary Liversidge, John Vincent Forrester

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Dendritic cells (DC) are key regulators of adaptive immunity with the potential to induce T cell activation/immunity or T cell suppression/tolerance. DC are themselves induced by "maturation" signals such as bacterial lipopolysaccharide (LPS). We demonstrate here that LPS can stimulate DC to display similar maturation phenotypes but to differentiate toward an interleukin (IL)10(high)- or IL-12(high)-Secretor profile depending on the tinting of maturation signal induction. Immediate/early administration of LPS induced purified bone marrow-derived DC (BMDC) to differentiate as IL-10(high)IL-12(low)-secreting cells, termed early DC (eDC). Conversely, delayed administration of LPS altered the DC cytokine profile to IL-10(low)IL-12(high), termed later DC (IDC). The presence of IL-4 enhanced the yield and maturation of BMDC but inhibited LPS-induced IL-10 production by eDC. In contrast, interferon-gamma reduced the yield of DC but promoted the level of LPS-induced IL-10 production by IDC. Our data provide new evidence that ex vivo manipulation and the cytokine enviromnent regulate DC maturation status and cytokine-secretor phenotype with implications for the control of T cell differentiation and function via DC-based immonotherapeutic strategies.

Original languageEnglish
Pages (from-to)978-985
Number of pages7
JournalJournal of Leukocyte Biology
Volume72
Issue number5
Publication statusPublished - Nov 2002

Keywords

  • bone marrow
  • cytokine-secretion profile
  • maturation status
  • BONE-MARROW CULTURES
  • SURVIVAL IN-VIVO
  • T-HELPER CELL
  • MATURATION-RESISTANT
  • ANTIGEN PRESENTATION
  • LARGE NUMBERS
  • GM-CSF
  • GENERATION
  • IMMATURE
  • IMMUNOTHERAPY

Cite this

Secretion of interleukin-10 or interleukin-12 by LPS-activated dendritic cells is critically dependent on time of stimulus relative to initiation of purified DC culture. / Jiang, Hui-Rong; Muckersie, Elizabeth; Robertson, Marie; Xu, Heping; Liversidge, Janet Mary; Forrester, John Vincent.

In: Journal of Leukocyte Biology, Vol. 72, No. 5, 11.2002, p. 978-985.

Research output: Contribution to journalArticle

Jiang, Hui-Rong ; Muckersie, Elizabeth ; Robertson, Marie ; Xu, Heping ; Liversidge, Janet Mary ; Forrester, John Vincent. / Secretion of interleukin-10 or interleukin-12 by LPS-activated dendritic cells is critically dependent on time of stimulus relative to initiation of purified DC culture. In: Journal of Leukocyte Biology. 2002 ; Vol. 72, No. 5. pp. 978-985.
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AU - Liversidge, Janet Mary

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N2 - Dendritic cells (DC) are key regulators of adaptive immunity with the potential to induce T cell activation/immunity or T cell suppression/tolerance. DC are themselves induced by "maturation" signals such as bacterial lipopolysaccharide (LPS). We demonstrate here that LPS can stimulate DC to display similar maturation phenotypes but to differentiate toward an interleukin (IL)10(high)- or IL-12(high)-Secretor profile depending on the tinting of maturation signal induction. Immediate/early administration of LPS induced purified bone marrow-derived DC (BMDC) to differentiate as IL-10(high)IL-12(low)-secreting cells, termed early DC (eDC). Conversely, delayed administration of LPS altered the DC cytokine profile to IL-10(low)IL-12(high), termed later DC (IDC). The presence of IL-4 enhanced the yield and maturation of BMDC but inhibited LPS-induced IL-10 production by eDC. In contrast, interferon-gamma reduced the yield of DC but promoted the level of LPS-induced IL-10 production by IDC. Our data provide new evidence that ex vivo manipulation and the cytokine enviromnent regulate DC maturation status and cytokine-secretor phenotype with implications for the control of T cell differentiation and function via DC-based immonotherapeutic strategies.

AB - Dendritic cells (DC) are key regulators of adaptive immunity with the potential to induce T cell activation/immunity or T cell suppression/tolerance. DC are themselves induced by "maturation" signals such as bacterial lipopolysaccharide (LPS). We demonstrate here that LPS can stimulate DC to display similar maturation phenotypes but to differentiate toward an interleukin (IL)10(high)- or IL-12(high)-Secretor profile depending on the tinting of maturation signal induction. Immediate/early administration of LPS induced purified bone marrow-derived DC (BMDC) to differentiate as IL-10(high)IL-12(low)-secreting cells, termed early DC (eDC). Conversely, delayed administration of LPS altered the DC cytokine profile to IL-10(low)IL-12(high), termed later DC (IDC). The presence of IL-4 enhanced the yield and maturation of BMDC but inhibited LPS-induced IL-10 production by eDC. In contrast, interferon-gamma reduced the yield of DC but promoted the level of LPS-induced IL-10 production by IDC. Our data provide new evidence that ex vivo manipulation and the cytokine enviromnent regulate DC maturation status and cytokine-secretor phenotype with implications for the control of T cell differentiation and function via DC-based immonotherapeutic strategies.

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KW - ANTIGEN PRESENTATION

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